Postmenopozal Türk Kadınlarında Osteoporotik Kırık Gelişiminde Kollajen I A 1 ve Vitamin D Reseptör Gen Polimorfizmlerinin Rolü

Abstract

Bu çalışmanın amacı postmenopozal Türk kadınlarında COLIA1 Spl ve VDR BsmI polimorfizmi ve kırık riski arasındaki ilişkiyi araştırmaktır. Aralarında akrabalık bulunmayan 90 kadın bu çalışmaya alındı. Tüm hastalar postmenapozal dönemde idi. Osteoporoz tanısı WHO kriterlerine göre koyuldu. Bu hastaların 30’ unda osteoporoz mevcuttu ve kalça ve/veya vertebral fraktür gelişmişti, 30 hastada osteoporoz mevcut ancak fraktür öyküsü yoktu, 30 hasta bu hastalarla aynı yaş grubunda idi ve osteoporoz ve fraktür mevcut değildi. COLIA1 gen polimorfizmi SS, Ss and ss olarak, VDR BsmI gen polimorfizmi BB, Bb, and bb olarak tanımlandı. Çalışma grubunun genotipik dağılımı ile BMD ve fraktür varlığı arasındaki ilişki istatistiksel olarak değerlendirildi. Gruplara göre COLIA1 Spl allel dağılımı değerlendirildiğinde alicilerinin sıklığı açısından gruplar arasında istatistiksel olarak anlamlı farklılığın olmadığı görüldü (p= 0.092). Benzer şekilde VDR BsmI allel dağılımı değerlendirildiğinde, alellerinin sıklığı üç grupta da benzerdi (p= 0.563). COLIA1 Spl ve VDR BsmI allel dağılımının kırık varlığı ile ilişkisinin değerlendirilmesinde Grup 2+Grup 3 verileri Grup 1 ile karşılaştırıldı. Buna göre COLIA1 ve VDR gen polimorfizmlerinin sıklığı açısından gruplar arasında farklılık olmadığı izlendi (COLIA1 için, p=0.352; VDR için, p= 0.946). Benzer şekilde osteoporoz varlığı ile allel dağılımının ilişkisini değerlendirmek için Grupl+Grup2 verileri Grup 3 ile karşılaştırıldı. Her iki gene ait allel dağılımları için gruplar arasında anlamlı fark saptanmadı (COLIA1 için, p=0.436; VDR için, p=0.635). Sonuç olarak postmenopozal Türk kadınlarında COLIA1 ve VDR genleri osteoporoz ve kırık riski ile ilişkili bulunmamıştır.

Keywords

• Osteoporoz; fraktür; COLIA1; vitamin D reseptörü
• Osteoporoz; fraktür
• COLIA1
• vitamin D reseptörü

The Role of Collagen I A 1 and Vitamin D Receptor Genes Polymorphisms on the Risk of Osteoporotic Fractures in Postmenopausal Turkish Women

Abstract

The objective of this study was to investigate the relationship between COLIA 1 Spl and VDR BsmI polymorphisms and fracture risk in postmenopausal Turkish women. Ninety unrelated females were included in this study. All of these patients were in postmenopausal period. The diagnosis of osteoporosis was done according to WHO criteria. Thirty of them had osteoporosis and also with hip and/or vertebral fracture, 30 of them had osteoporosis but without fracture history and 30 individuals in similar age group had neither osteoporosis nor fracture. COLIA 1 gene polymorphisms were defined as SS, Ss, and ss. VDR BsmI gene polymorphisms were defined as BB, Bb, and bb. The relationship between genotypic distribution, BMD, and presence of fracture was evaluated statistically. When distribution of COLIA Spl allele was evaluated according to groups, there was no statistically significant difference in frequency of alleles between the groups (p=0.092). Also VDR BsmI allele distribution was evaluated, in all 3 groups frequency of alleles was similar (p=0.563). Relationship between COLIA1 Spl and VDR BsmI allele distribution and presence of fracture was evaluated. Data of Group II and Group III was compared with data of Group I. There was no difference in frequency of COLIA 1 and VDR gene polymorphisms between these groups (for COLIA1 p=0.352, for VDR p=0.946). Similarly relationship between presence of osteoporosis and allele distribution was evaluated. Data of Group I +Group II was compared with data of Group III. Allele distribution of both genes was not significantly different in groups (for COLIA 1 p=0.436. for VDR p=0.635). In conclusion, COLIA1 and VDR genes are not associated with fracture risk and BMD in postmenopausal Turkish women. Reyhan ERSOY, Bekir ÇAKIR, Mahmut UĞURLU, Oya TOPALOĞLU, Ayşenur UĞURLU, MD, Meryem KURU, Kasım KILIÇARSLAN, Bülent BEKTAŞER, Semra BAYKAL, Mehmet GÜMÜŞ,

Keywords

• Osteoporosis; fracture; COLIA1; Vitamin D Receptor
• ,genses
• a1,

References

1. 1. Kanis JA, Melton III LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994; 9:1137-1141
2. 2. Ralston SH. Genetic control of susceptibility to osteoporosis. J Clin Endocrinol Metab 2002; 87:2460-6.
3. 3. Grant SFA, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH. Reduced bone density and osteoporosis associated with a polymorphic Sp1 site in the collagen type 1 a1 gene. Nat Genet 1996; 14:203-205
4. 4. Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP et al. A COLIA1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 2001; 107:899-907.
5. 5. Pike JW, Yamamoto H, Shevde NK. Vitamin D receptor- mediated gene regulation mechanisms and current concepts of vitamin D analog selectivity. Adv Ren Replace Ther 2002; 9:168-174
6. 6. Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, et al. Prediction of bone density from vitamin D receptor alleles. Nature 1994; 367:284-287
7. 7. Uitterlinden AG, Burger H, Huang Q, Yue F, McGuigan FE, Grant SF, et al. Relation of alleles of the collagen type 1a1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women. N Engl J Med 1998; 338:1016-1021
8. 8. Uitterlinden AG, Weel AE, Burger H, Fang Y , Van Dujin CM, Hofman A, et al. Interaction between the Vitamin D receptor gene and collagen type 1a1 gene in susceptibility for fracture. J Bone Miner Res 2001; 16:379-85.

9. 9. Langdahl BL, Ralston SH, Grant SF, Eriksen EF. An Sp1 binding site polymorphism in the COLIA1 gene predicts osteoporotic fractures in both men and women. J Bone Miner Res 1998; 13:1384-9.
10. 10. Aerssens J, Dequeker J, Peeters J, Breemans S, Broos P, Boonen S. Polymorphisms of the VDR, ER, and COLIA1 genes and osteoporotic fracture in elderly postmenopausal women. Osteoporosis I nt 2000; 11:583-91.
11. 11. Valimaki S, Tahtela R, Kainulainen K, Laitinen K, Loyttyniemi E, Sulkava R, et al. Relation of collagen type 1a1 (COLIA1) and Vitamin D receptor genotypes to bone mass, turnover, and fractures in early postmenopausal women and to hip fractures in elderly people. Eur J Int Med 2001; 12:48-56. Ensurd KE, Stone K, Cauley JA, White C, Zmuda JM, Nguyen TV, et al. Vitamin D receptor gene polymorphisms and the risk of fractures in older women. For the Study of Osteoporotic Fractures Research Group. J Bone Miner Res 1999;14:1637-45.
12. 13. World Health Organization, Guidelines for Preclini-cal Evaluation and Clinical Trials in Osteoporosis, WHO, Geneva (1998).
13. 14. Beavan S, Prentice A, Dibba B, Yan L, Cooper C, Ralston SH. Polymorphism of the collogen type I a1 gene and ethnic differences in hip fracture rates. N Engl J Med 1998;339:351-2.
14. 15. Ralston SH, Uitterlinden AG, Brandi ML, Balcells S, Langdahl BL, Lips P, et al. Large- Scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: The GENOMOS Study. Pios Med 2006; 4:515-23.
15. 16. Bemad M, Martinez ME, Escalona M, Gonzalez ML, Garces MV, et al. Polymorphism in the type I collogen (COLIA1) gene and risk of fractures in postmenopausal women. Bone 2002; 30:223-8.
16. 17. Hubacek JA, Weichetova M, Bohuslavova R, Skodova Z, Stephan JJ, Adamkova V. No associations between genetic polymorphisms of TGF-p, PAI-1, and COLIA1, and bone mineral density in Caucasian females. Endocrine Regulations 2006; 40:107-12.
17. 18. Barros ER, Kasamatsu TS, Ramalho AC, Hauache OM, Vieria JGH, Lazeretti-Castro M. Bone mineral density in young women of the city of Sao Paulo, Brazil: correlation with both collogen type I alpha 1 gene polymorphism and clinical aspects. Braz J Med Biol Res 2002; 8:885-93.
18. 19. Linden M, Wilen B, Ljunghall S, Melhus H. Polymorphism at the Sp 1 binding site in the collogen type 1 alpha 1 gene does not predict bone density in postmenopausal women in Sweden. Calcified Tissue International 1998; 63:293-5.
19. 20. Garnero P, Munoz F, Borel O, Sornay-Rendu E, Delmas PD. Vitamin D receptor gene polymorphisms are associated with the risk of fractures in postmenopausal women, independently of bone mineral density. J Clin Endocrinol Metab 2005; 90:4829-35.
20. 21. Langdahl BL, Gravholt CH, Brixen K, Eriksen EF. Polymorphisms in the vitamin D receptor gene and bone mass, bone turnover and osteoporotic fractures. Eur J Clin Invest 2000; 30:608-17.
21. 22. Feskanich D, Hunter DJ, Willett WC, Hankinson SE, Hollis BW, Hough HL, et al. Vitamin D receptor genotype and the risk of bone fractures in women. Epidemiology 1998; 9:535-539
22. 23. Colin EM, Uitterlinden AG, Meurs JBJ, Bergink AP, Klift M van de, Fang Y, et al. Interaction between Vitamin D receptor genotype and estrogen receptor a genotype influences vertebral fracture risk. J Clin Endocrinol Metab 2003; 88:3777-84.
23. 24. Dündar U, Solak M, Kavuncu V, Ozdemir M, Cakir T, Yildiz H, et al. Evidence of association of Vitamin D receptor Apa I gene polymorphism with bone mineral density in postmenopausal women with osteoporosis. Clin Rheumatol 2009; 28:1187-91.